Liver — Nutrient Metabolism

Anabolic Role

Synthesis or lipoproteins for transport of lipids from dietary FFA’s

• Chylomicrons
• LDL/HDLs

Lipogenesis via citrate in the TCA:

• Citrate leaves mitochondria and is converted back to Acetyl-CoA
• Acetyl-CoA goes to Malonyl-CoA (conversion ↑d by insulin)
• Fatty acids: via fatty acyl-CoA
  • Malonyl-CoA → Fatty-Acyl CoA in the reverse of B-oxidation and creates Triglycerides
• Cholesterol: via HMG-CoA
  • blocked by statins

Catabolic Role

Β-oxidation:

• FACoA synthase in cytosol makes FACoA
• FACoA → Acyl carnitine by CPT1 and transported into cell
• Acyl carnitine → FACoA by CPT2
• Undergoes B oxidation
  • 1 Acetyl CoA (by cleaving the 2 carbon-CoA from the whole molecule) → Used in TCA cycle
  • 1 FADH2 + 1 NADH to be used in the Electron Transport Chain.
• → up to 17 molecules of ATP

Anabolic Role

Glucostat Function

• Gluconeogenesis from pyruvate derived from
  • Complex polysaccharides (fructose and galactose)
  • Glycogen
  • Gluconeogenesis
  • lactate, pyruvate, glycerol (from TAGs), glucogenic a.a’s (esp Ala and Glu)
  • Pentose phosphate shunt
  • Glycerol (but not FFAs)
• Glycogen synthesis

Catabolic Role

Glycolysis:

• Primary function
• For generation of pyruvate + 2 ATP
• Pyruvate then utilised to form
  • fat, AA’s and ketones
  • Lactate

Glycogenolysis:

• From G6P.

Anabolic Role

Generation of functional proteins in serum:

• Albumin
• Fibrinogen
• Coagulation proteins
• Regulatory proteins
  • Coagulation factors
  • Complement proteins
• Globulins
  • α1 (α1 anti-trypsin, α1-fetoprotein)
  • α2 (haptoglobulin),
  • β (transferrin)

Amino acids and nucleosides from α-ketogluterate in the TCA

Haeme from Succinyl-CoA in the TCA

Catabolic Role

• Breakdown of proteins to form
  • ketones as energy source (liver, heart and brain)
  • free amino acids for addition to the AA pool.
• Amino acids utilisation for energy or protein synthesis
• Ammonia metabolism and recycling
• Deamination of fatty acids 
• Urea formation for ammonia removal Part of the urea cycle takes place in liver